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Structure of the extended-spectrum ?-lactamase TEM-72 inhibited by citrate.

ABSTRACT: TEM-72, a class A ?-lactamase identified in isolates of Enterobacteriaceae, is a quadruple mutant of TEM-1 (Q39K, M182T, G238S and E240K) and shows extended-spectrum ?-lactamase (ESBL) properties arising from the G238S and E240K substitutions. Although many structures of TEM variants have been published, they do not include an enzyme with the simultaneous presence of both of the ESBL-conferring G238S and E240K substitutions. Furthermore, the structure shows the presence of a citrate anion bound to the TEM-72 active site, where it interacts with all of the conserved residues of class A ?-lactamases. The present structure supports the use of polycarboxylates as a scaffold for the design of broad-spectrum inhibitors of serine ?-lactamases.

SUBMITTER: Docquier JD

PROVIDER: S-EPMC3053151 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Structure of the extended-spectrum β-lactamase TEM-72 inhibited by citrate.

Docquier Jean Denis JD Benvenuti Manuela M Calderone Vito V Rossolini Gian Maria GM Mangani Stefano S

Acta crystallographica. Section F, Structural biology and crystallization communications 20110218 Pt 3

TEM-72, a class A β-lactamase identified in isolates of Enterobacteriaceae, is a quadruple mutant of TEM-1 (Q39K, M182T, G238S and E240K) and shows extended-spectrum β-lactamase (ESBL) properties arising from the G238S and E240K substitutions. Although many structures of TEM variants have been published, they do not include an enzyme with the simultaneous presence of both of the ESBL-conferring G238S and E240K substitutions. Furthermore, the structure shows the presence of a citrate anion bound ...[more]

PMID: 21393831

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